The cross-talk between several parts of the gut and the brain involves the exchange of information that enables an individual to optimize metabolism and to adapt it to potentially huge variations in caloric intake during, e.g. fasting and eating. It also ensures that already parts of the gut downstream of the oropharynx are informed about what kind of food will arrive soon and what to do with it. These phenomena are largely mysteries to us, but some light is shed over these fields. This review will address some of the developments that illustrate how sophisticated these ancient mechanism of cross-talk are and what they could mean to us as highly developed 'modern' mammals.